tbuckley/cabot-search huggingface dataset:
The gut-microbiota-brain axis in a Spanish population in the aftermath of the COVID-19 pandemic: microbiota composition linked to anxiety, trauma, and depression profiles
Authors: Stefanie Malan-Müller, Mireia Valles-Colomer, Tomás Palomo, Juan C. Leza
Journal: Gut Microbes (2023)

The prevalence of anxiety and depression soared following the COVID-19 pandemic. To effectively treat these conditions, a comprehensive understanding of all etiological factors is needed. This study investigated fecal microbial features associated with mental health outcomes (symptoms of anxiety, depression, or posttraumatic stress disorder (PTSD)) in a Spanish cohort in the aftermath of the COVID-19 pandemic. Microbial communities from stool samples were profiled in 198 individuals who completed validated, self-report questionnaires. 16S ribosomal RNA gene V3-4 amplicon sequencing was performed. Microbial diversity and community structure were analyzed, together with relative taxonomic abundance. In our cohort of N=198, 17.17% reported depressive symptoms, 37.37% state anxiety symptoms, 40.90% trait anxiety symptoms, and 8.08% PTSD symptoms, with high levels of comorbidity. Individuals with trait anxiety had lower Simpson's diversity. Fusicatenibacter saccharivorans was reduced in individuals with comorbid PTSD + depression + state and trait anxiety symptoms, whilst an expansion of Proteobacteria and depletion of Synergistetes phyla were noted in individuals with depressive symptoms. The relative abundance of Anaerostipes was positively correlated with childhood trauma, and higher levels of Turicibacter sanguinis and lower levels of Lentisphaerae were found in individuals who experienced life-threatening traumas. COVID-19 infection and vaccination influenced the overall microbial composition and were associated with distinct relative taxonomic abundance profiles. These findings will help lay the foundation for future studies to identify microbial role players in symptoms of anxiety, depression, and PTSD and provide future therapeutic targets to improve mental health outcomes.
How are covid-19 symptoms changing?
Authors: Mun-Keat Looi
Journal: BMJ (2023)

How are covid-19 symptoms changing?With new variants and a changing landscape of vaccination and immunity, what do the symptoms of covid-19-and our understanding of them-now look like?Mun-Keat Looi reports Mun-Keat Looi international features editorHow have covid symptoms changed since the start of the pandemic?In the short space of a few years we've seen surprising changes in the way covid-19 presents.At the start of the pandemic the first commonly reported symptoms were loss of smell and taste, followed by shortness of breath and a cough, followed by vascular injuries, says David Strain, senior clinical lecturer at the University of Exeter Medical School."That became the standard that we expected," he says.Betty Raman, senior clinical research fellow in the Radcliffe Department of Medicine, University of Oxford, says, "People presenting with the earlier variants would have quite severe cardiorespiratory or mostly respiratory symptoms in the acute phase with other symptoms too, like brain fog.Quite a significant proportion were admitted to hospital with the earlier variants.
Author Correction: Transmission of trained immunity and heterologous resistance to infections across generations
Authors: Natalie Katzmarski, Jorge Domínguez-Andrés, Branko Cirovic, Georgios Renieris, Eleonora Ciarlo, Didier Le Roy, Konstantin Lepikhov, Kathrin Kattler, Gilles Gasparoni, Kristian Händler, Heidi Theis, Marc Beyer, Jos W. M. van der Meer, Leo A. B. Joosten, Jörn Walter, Joachim L. Schultze, Thierry Roger, Evangelos J. Giamarellos-Bourboulis, Andreas Schlitzer, Mihai G. Netea
Journal: Nature Immunology (2023)
Sara Suliman: Science is better when it’s shared
Authors: Lucie Van Emmenis
Journal: The Journal of Experimental Medicine (2023)

Sara Suliman is an assistant professor in the Department of Experimental Medicine at the University of California, San Francisco (UCSF). Her lab uses multiple approaches to identify candidate tuberculosis (TB) risk pathways and to determine their role in TB progression. I caught up with Sara to talk about how she got interested in science, what she's currently working on, and what she thinks about the future of academic science.
Experimental encephalomyelitis at age 90, still relevant and elucidating how viruses trigger disease
Authors: Lawrence Steinman, Roberto Patarca, William Haseltine
Journal: The Journal of Experimental Medicine (2023)

20 yr ago, a tribute appeared in this journal on the 70th anniversary of an animal model of disseminated encephalomyelitis, abbreviated EAE for experimental autoimmune encephalomyelitis. "Observations on Attempts to Produce Disseminated Encephalomyelitis in Monkeys" appeared in the Journal of Experimental Medicine on February 21, 1933. Rivers and colleagues were trying to understand what caused neurological reactions to viral infections like smallpox, vaccinia, and measles, and what triggered rare instances of encephalomyelitis to smallpox vaccines. The animal model known as EAE continues to display its remarkable utility. Recent research, since the 70th-anniversary tribute, helps explain how Epstein-Barr virus triggers multiple sclerosis via molecular mimicry to a protein known as GlialCAM. Proteins with multiple domains similar to GlialCAM, tenascin, neuregulin, contactin, and protease kinase C inhibitors are present in the poxvirus family. These observations take us a full circle back to Rivers' first paper on EAE, 90 yr ago.
Cell autonomous expression of BCL6 is required to maintain lineage identity of mouse CCR6+ ILC3s
Authors: Yuling Li, Jing Ge, Xiaohong Zhao, Miao Xu, Mengting Gou, Bowen Xie, Jinling Huang, Qinli Sun, Lin Sun, Xue Bai, Sangnee Tan, Xiaohu Wang, Chen Dong
Journal: The Journal of Experimental Medicine (2023)

Innate lymphoid cells (ILC) are similar to T helper (Th) cells in expression of cytokines and transcription factors. For example, RORγt is the lineage-specific transcription factor for both ILC3 and Th17 cells. However, the ILC counterpart for BCL6-expressing T follicular helper (Tfh) cells has not been defined. Here, we report that in the ILC compartment, BCL6 is selectively co-expressed with not only CXCR5 but also RORγt and CCR6 in ILC3 from multiple tissues. BCL6-deficient ILC3 produces enhanced levels of IL-17A and IL-22. More importantly, phenotypic and single-cell ATAC-seq analysis show that absence of BCL6 in mature ILC3 increases the numbers of ILC1 and transitional cells co-expressing ILC3 and ILC1 marker genes. A lineage-tracing experiment further reveals BCL6+ ILC3 to ILC1 trans-differentiation under steady state. Finally, microbiota promote BCL6 expression in colonic CCR6+ ILC3 and thus reinforce their stability. Collectively, our data have demonstrated that CCR6+ ILC3 have both Th17 and Tfh programs and that BCL6 expression in these cells functions to maintain their lineage identity.
Romidepsin-CHOEP followed by high-dose chemotherapy and stem-cell transplantation in untreated Peripheral T-Cell Lymphoma: results of the PTCL13 phase Ib/II study
Authors: Annalisa Chiappella, Anna Dodero, Andrea Evangelista, Alessandro Re, Lorella Orsucci, Sara Veronica Usai, Claudia Castellino, Vittorio Stefoni, Antonio Pinto, Manuela Zanni, Rosanna Ciancia, Chiara Ghiggi, Francesca Gaia Rossi, Annalisa Arcari, Fiorella Ilariucci, Vittorio Ruggero Zilioli, Leonardo Flenghi, Melania Celli, Stefano Volpetti, Fabio Benedetti, Filippo Ballerini, Gerardo Musuraca, Riccardo Bruna, Caterina Patti, Francesco Leonardi, Luca Arcaini, Massimo Magagnoli, Federica Cavallo, Anisa Bermema, Alessandra Tucci, Carola Boccomini, Giovannino Ciccone, Cristiana Carniti, Stefano Aldo Pileri, Paolo Corradini
Journal: Leukemia (2023)

Abstract The standard treatment for young patients with untreated PTCLs is based on anthracycline containing-regimens followed by high-dose-chemotherapy and stem-cell-transplantation (HDT + SCT), but only 40% of them can be cured. Romidepsin, a histone-deacetylase inhibitor, showed promising activity in relapsed PTCLs; in first line, Romidepsin was added with CHOP. We designed a study combining romidepsin and CHOEP as induction before HDT + auto-SCT in untreated PTCLs (PTCL-NOS, AITL/THF, ALK-ALCL), aged 18–65 years. A phase Ib/II trial was conducted to define the maximum tolerated dose (MTD) of Ro-CHOEP, and to assess efficacy and safety of 6 Ro-CHOEP as induction before HDT. The study hypothesis was to achieve a 18-month PFS of 70%. Twenty-one patients were enrolled into phase Ib; 7 dose-limiting toxicities were observed, that led to define the MTD at 14 mg/ms. Eighty-six patients were included in the phase II. At a median follow-up of 28 months, the 18-month PFS was 46.2% (95%CI:35.0–56.7), and the 18-month overall survival was 73.1% (95%CI:61.6–81.7). The overall response after induction was 71%, with 62% CRs. No unexpected toxicities were reported. The primary endpoint was not met; therefore, the enrollment was stopped at a planned interim analysis. The addition of romidepsin to CHOEP did not improve the PFS of untreated PTCL patients.
Comparison of the clinical and virological characteristics of SARS-CoV-2 Omicron BA.1/BA.2 and omicron BA.5 variants: A prospective cohort study
Authors: Sung-Woon Kang, Heedo Park, Ji Yeun Kim, So Yun Lim, Sohyun Lee, Joon-Yong Bae, Jeonghun Kim, Euijin Chang, Seongman Bae, Jiwon Jung, Min Jae Kim, Yong Pil Chong, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Man-Seong Park, Sung-Han Kim
Journal: Journal of Infection (2023)
Downregulation of G protein–coupled receptor kinase 4 protects against kidney ischemia-reperfusion injury
Authors: Donghai Yang, Ming Tang, Mingming Zhang, Hongmei Ren, Xiaoping Li, Ziyue Zhang, Bo He, Song Peng, Wei Wang, Dandong Fang, Yi Song, Yao Xiong, Zhi Zhao Liu, Lijia Liang, Weibin Shi, Chunjiang Fu, Yijie Hu, Pedro A. Jose, Lin Zhou, Yu Han, Chunyu Zeng
Journal: Kidney International (2023)
Zero‐Valence Selenium‐Enriched Prussian Blue Nanozymes Reconstruct Intestinal Barrier against Inflammatory Bowel Disease via Inhibiting Ferroptosis and T Cells Differentiation
Authors: Dongdong Zhu, Haitao Wu, Kai Jiang, Yifeng Xu, Zhaohua Miao, Hua Wang, Yan Ma
Journal: Advanced Healthcare Materials (2023)

Abstract The structural disruption of mechanical barrier and dysfunction of immune barrier in intestinal, are important factors, that aggravate inflammatory bowel disease (IBD). To tackle this challenge, a multifunctional nanozyme capable of scavenging reactive oxygen species (ROS) and inhibiting ferroptosis or T cells differentiation for IBD therapy is here reported. In this work, zero‐valence selenium‐enriched Prussian blue nanozymes (Se‐HMPB nanozymes) are prepared via the hard template method. PB nanozymes with multi‐enzyme activities can effectively scavenge various ROS in inflammatory tissues. Meanwhile, the presence of selenium element endows the glutathione peroxidase activity of Se‐HMPB nanozymes, which can inhibit ferroptosis and reverse the lipid peroxidation of intestinal epithelial cells to protect the intestinal mechanical barrier in ulcerative colitis (UC) model. In addition, selenium supplementation can realize efficient inhibition on the differentiation of T cells in Crohn's disease (CD) model, regulating the intestinal immune barrier. Thus, the Se‐HMPB nanozymes reconstructed intestinal barrier via inhibiting ferroptosis and T cells differentiation in UC and CD models, depicting great potential to alleviate IBD.
Capsaicin receptor TRPV1 maintains quiescence of hepatic stellate cells in the liver via recruitment of SARM1
Authors: Le Tao, Guangyue Yang, Tiantian Sun, None Jie Tao, Chan Zhu, Huimin Yu, Yalan Cheng, Zongguo Yang, Mingyi Xu, Yuefeng Jiang, Wei Zhang, Zhiyi Wang, Wenting Ma, Liu Wu, Dongying Xue, Dongxue Wang, Wentao Yang, Yongjuan Zhao, Shane Horsefield, Bostjan Kobe, Zhe Zhang, Zongxiang Tang, Qigen Li, Qiwei Zhai, Steven Dooley, Ekihiro Seki, Ping Liu, Jianrong Xu, Hongzhuan Chen, Cheng Liu
Journal: Journal of Hepatology (2023)
Frequency and reliability of histologic subtype classification in invasive and in situ melanoma treated with Mohs micrographic surgery
Authors: Carolyn M. Stull, Shannon T. Nugent, Leela K. Raj, Joseph F. Sobanko, Thuzar M. Shin, Jeremy R. Etzkorn, Harold W. Higgins, Cerrene N. Giordano, Stacy L. McMurray, Joanna L. Walker, Christopher J. Miller
Journal: Journal of the American Academy of Dermatology (2023)
Modelling the potential effectiveness of hepatitis C screening and treatment strategies during pregnancy in Egypt and Ukraine
Authors: Nadia Hachicha-Maalej, Intira Jeannie Collins, Anthony E. Ades, Karen Scott, Ali Judd, Aya Mostafa, Elizabeth Chappell, Manal Hamdy-El-Sayed, Diana Gibb, Sarah Pett, Eugènia Mariné-Barjoan, Alla Volokha, Yazdan Yazdanpanah, Sylvie Deuffic-Burban
Journal: Journal of Hepatology (2023)

HCV test and treat campaigns currently exclude pregnant women. Pregnancy offers a unique opportunity for HCV screening and to potentially initiate direct-acting antiviral treatment. We explored HCV screening and treatment strategies in two lower middle-income countries with high HCV prevalence, Egypt and Ukraine.
Explainable artificial intelligence for mental health through transparency and interpretability for understandability
Authors: Dan W. Joyce, Andrey Kormilitzin, Katharine A. Smith, Andrea Cipriani
Journal: npj Digital Medicine (2023)

Abstract The literature on artificial intelligence (AI) or machine learning (ML) in mental health and psychiatry lacks consensus on what “explainability” means. In the more general XAI (eXplainable AI) literature, there has been some convergence on explainability meaning model-agnostic techniques that augment a complex model (with internal mechanics intractable for human understanding) with a simpler model argued to deliver results that humans can comprehend. Given the differing usage and intended meaning of the term “explainability” in AI and ML, we propose instead to approximate model/algorithm explainability by understandability defined as a function of transparency and interpretability. These concepts are easier to articulate, to “ground” in our understanding of how algorithms and models operate and are used more consistently in the literature. We describe the TIFU (Transparency and Interpretability For Understandability) framework and examine how this applies to the landscape of AI/ML in mental health research. We argue that the need for understandablity is heightened in psychiatry because data describing the syndromes, outcomes, disorders and signs/symptoms possess probabilistic relationships to each other—as do the tentative aetiologies and multifactorial social- and psychological-determinants of disorders. If we develop and deploy AI/ML models, ensuring human understandability of the inputs, processes and outputs of these models is essential to develop trustworthy systems fit for deployment.
Circular RNAs at the intersection of cancer and heart disease: potential therapeutic targets in cardio-oncology
Authors: Dimyana Neufeldt, Sarah Cushman, Christian Bär, Thomas Thum
Journal: Cardiovascular Research (2023)

Abstract Considerable progress has been made in managing cancer; however, with these advancements comes the discovery of previously unknown adverse events. In particular, the prolonged lifespan of patients has uncovered severe cardiotoxic side effects of widely used anti-cancer therapies, which restrict their administration and thus compromise the success of the seemingly most suitable treatments in large cancer patient cohorts. Vice versa, cardiovascular diseases can also promote both the onset and progression of different cancers, highlighting that both conditions are deeply interlinked. Recognizing these close interactions, the novel interdisciplinary field of cardio-oncology has emerged to closely study these uniquely correlating diseases. In this regard, non-coding RNAs (ncRNAs) are gaining increasing attention since they constitute crucial regulators in many physiological but also pathological signalling pathways, including those of cancer and cardiac dysfunction. In this review, we focus on the new subtype of ncRNA, circular RNAs, in their distinct exchange within cardio-oncology and discuss their suitability as potent targets for the simultaneous treatment of cardiac dysfunction and cancer.
PTX3 from vascular endothelial cells contributes to trastuzumab-induced cardiac complications
Authors: Zhifei Xu, Zizheng Gao, Huangxi Fu, Yan Zeng, Ying Jin, Bo Xu, Yuanteng Zhang, Zezheng Pan, Xueqin Chen, Xiaochen Zhang, Xiaohong Wang, Hao Yan, Xiaochun Yang, Bo Yang, Qiaojun He, Peihua Luo
Journal: Cardiovascular Research (2023)

Trastuzumab, the first humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (ERBB2/HER2), is currently used as a first-line treatment for HER2 (+) tumours. However, trastuzumab increases the risk of cardiac complications without affecting myocardial structure, suggesting a distinct mechanism of cardiotoxicity.We used medium from trastuzumab-treated human umbilical vein endothelial cells (HUVECs) to treat CCC-HEH-2 cells, the human embryonic cardiac tissue-derived cell lines, and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to assess the crosstalk between vascular endothelial cells (VECs) and cardiomyocytes. Protein mass spectrometry analysis was used to identify the key factors from VECs that regulate the function of cardiomyocytes. We applied RNA-sequencing to clarify the mechanism, by which PTX3 causes cardiac dysfunction. We used an anti-human/rat HER2 (neu) monoclonal antibody to generate a rat model that was used to evaluate the effects of trastuzumab on cardiac structure and function and the rescue effects of lapatinib on trastuzumab-induced cardiac side effects. Medium from trastuzumab-treated HUVECs apparently impaired the contractility of CCC-HEH-2 cells and iPSC-CMs. PTX3 from VECs caused defective cardiomyocyte contractility and cardiac dysfunction in mice, phenocopying trastuzumab treatment. PTX3 affected calcium homoeostasis in cardiomyocytes, which led to defective contractile properties. EGFR/STAT3 signalling in VECs contributed to the increased expression and release of PTX3. Notably, lapatinib, a dual inhibitor of EGFR/HER2, could rescue the cardiac complications caused by trastuzumab by blocking the release of PTX3.We identified a distinct mode of cardiotoxicity, wherein the activation of EGFR/STAT3 signalling by trastuzumab in VECs promotes PTX3 excretion, which contributes to the impaired contractility of cardiomyocytes by inhibiting cellular calcium signalling. We confirmed that lapatinib could be a feasible preventive agent against trastuzumab-induced cardiac complications and provided the rationale for the combined application of lapatinib and trastuzumab in cancer therapy.
Sex differences and disparities in cardiovascular outcomes of COVID-19
Authors: Raffaele Bugiardini, Stefano Nava, Gaetano Caramori, Jinsung Yoon, Lina Badimon, Maria Bergami, Edina Cenko, Antonio David, Ilir Demiri, Maria Dorobantu, Oana Fronea, Radmilo Jankovic, Sasko Kedev, Nebojsa Ladjevic, Ratko Lasica, Goran Loncar, Giuseppe Mancuso, Guiomar Mendieta, Davor Miličić, Petra Mjehović, Marijan Pašalić, Milovan Petrović, Lidija Poposka, Marialuisa Scarpone, Milena Stefanovic, Mihaela van der Schaar, Zorana Vasiljevic, Marija Vavlukis, Maria Laura Vega Pittao, Vladan Vukomanovic, Marija Zdravkovic, Olivia Manfrini
Journal: Cardiovascular Research (2023)

Previous analyses on sex differences in case fatality rates at population-level data had limited adjustment for key patient clinical characteristics thought to be associated with coronavirus disease 2019 (COVID-19) outcomes. We aimed to estimate the risk of specific organ dysfunctions and mortality in women and men.This retrospective cross-sectional study included 17 hospitals within 5 European countries participating in the International Survey of Acute Coronavirus Syndromes COVID-19 (NCT05188612). Participants were individuals hospitalized with positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from March 2020 to February 2022. Risk-adjusted ratios (RRs) of in-hospital mortality, acute respiratory failure (ARF), acute heart failure (AHF), and acute kidney injury (AKI) were calculated for women vs. men. Estimates were evaluated by inverse probability weighting and logistic regression models. The overall care cohort included 4499 patients with COVID-19-associated hospitalizations. Of these, 1524 (33.9%) were admitted to intensive care unit (ICU), and 1117 (24.8%) died during hospitalization. Compared with men, women were less likely to be admitted to ICU [RR: 0.80; 95% confidence interval (CI): 0.71-0.91]. In general wards (GWs) and ICU cohorts, the adjusted women-to-men RRs for in-hospital mortality were of 1.13 (95% CI: 0.90-1.42) and 0.86 (95% CI: 0.70-1.05; pinteraction = 0.04). Development of AHF, AKI, and ARF was associated with increased mortality risk (odds ratios: 2.27, 95% CI: 1.73-2.98; 3.85, 95% CI: 3.21-4.63; and 3.95, 95% CI: 3.04-5.14, respectively). The adjusted RRs for AKI and ARF were comparable among women and men regardless of intensity of care. In contrast, female sex was associated with higher odds for AHF in GW, but not in ICU (RRs: 1.25; 95% CI: 0.94-1.67 vs. 0.83; 95% CI: 0.59-1.16, pinteraction = 0.04).Women in GW were at increased risk of AHF and in-hospital mortality for COVID-19 compared with men. For patients receiving ICU care, fatal complications including AHF and mortality appeared to be independent of sex. Equitable access to COVID-19 ICU care is needed to minimize the unfavourable outcome of women presenting with COVID-19-related complications.
The effectiveness of cell-derived exosome therapy for diabetic wound: A systematic review and meta-analysis
Authors: Zhihua Qiao, Xiancheng Wang, Hongli Zhao, Yiwen Deng, Weiliang Zeng, Kai Yang, Hui Chen, Quanding Yan, Chunjie Li, Jingjing Wu, Yunzhu Chen
Journal: Ageing Research Reviews (2023)

The prevalence of diabetes among the elderly population is significant and rising annually. One of the most severe and frequent complications of diabetes mellitus is the diabetic wound, which has long-term negative effects on patients' finances, mental health, and functional abilities. Exosomes, a cell-free therapy, have emerged as a promising novel treatment for diabetic wounds, but their mechanism is still not entirely understood. Therefore, we conducted this meta-analysis to assess the effectiveness of exosomes in the management of diabetic wounds.We searched PubMed, the Cochrane Library, EMBASE, and Web of Science for pertinent studies that described the therapeutic benefits of exosomes on diabetic wound models that were released before October 17, 2022. The outcome indicators consisted of wound healing rate, neovascular density, re-epithelialization rate, collagen deposition, scar width, and inflammatory factors. RevMan 5.4 software was used to conduct all statistical analyses.A total of 21 studies with 323 animals were identified in this meta-analysis. Pooled analyses demonstrated that exosome therapy was shown to be superior to control therapy in terms of wound healing rate (SMD = 5.42; 95 %CI = 4.40-6.44; P < 0.00001), neovascular density (SMD = 5.48; 95 %CI = 4.31-6.64; P < 0.00001), re-epithelialization rate (SMD = 5.06; 95 %CI = 3.75-6.37; P < 0.00001), collagen deposition (SMD = 4.78; 95 %CI = 3.58-5.98; P < 0.00001), scar width (SMD = -8.10; 95 %CI = -10.31 to -5.89; P < 0.00001). Additionally, the expression of inflammatory factors was significantly downregulated in the exosome treatment group.According to this meta-analysis of the current trials, exosome therapy can enhance the quality of diabetic wounds, especially when used in conjunction with novel dressings. To demonstrate the most efficient exosomes and therapeutic parameters for the treatment of diabetic wounds, future studies should conduct sizable, randomized, double-blind trials with high-quality, long-term follow-ups.